Factors affecting driving performance in patients with Multiple Sclerosis - still an open question.

Background and objectives: Research on driving ability in people with multiple sclerosis (MS) suggests that they might be at risk for unsafe driving due to MS-related motor, visual, and cognitive impairment. Our first aim was to investigate differences in driving ability and performance between people with MS (PwMS) and those without any neurologic or psychiatric disease ("controls"). Secondly, we determined disease-related factors influencing driving ability in PwMS. Methods: We prospectively compared standardized performance in a driving simulator between 97 persons with early MS [mean (SD) = 6.4 (7.3) years since diagnosis, mean (SD) Expanded Disability Status Scale (EDSS) = 2.5 (1.4)] and 94 group-matched controls. Participants completed an extensive examination comprising questionnaires and assessments regarding driving, cognitive and psychological factors, as well as demographic and disease-related measures. Between-group comparisons of driving-relevant neuropsychological tests and driving performance were done. Correlations were performed to define demographic and disease-related factors on driving performance in MS. Results: In a driving simulator setting, PwMS had more driving accidents [T(188) = 2.762, p = 0.006], reacted slower to hazardous events [T(188) = 2.561, p = 0.011], made more driving errors [T(188) = 2.883, p = 0.004] and had a worse Driving Safety Score (DSS) [T(188) = 3.058, p = 0.003] than controls. The only disease-related measure to be associated with most driving outcomes was the Wechsler Block-Tapping test (WMS-R) backward: number of accidents (r = 0.28, p = 0.01), number of driving errors (r = 0.23, p = 0.05) and DSS (r = -0.23, p = 0.05). Conclusion: Driving performance in a simulator seems to be reduced in PwMS at an early stage of disease compared to controls, as a result of increased erroneous driving, reduced reaction time and higher accident rate. MS-related impairment in mobility, vision, cognition, and in psychological and demographic aspects showed no or only minimal association to driving ability, but impairment in different areas of cognition such as spatial short-term memory, working memory and selective attention correlated with the number of accidents, and might indicate a higher risk for driving errors and worse performance. These results show that driving ability is a complex skill with involvement of many different domains, which need further research.

Cortical changes in patients with schizophrenia across two ethnic backgrounds.

While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.

E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials.

OBJECTIVES: To determine the effects of electronic cigarettes (e-cigarettes) as a therapeutic intervention compared to nicotine replacement therapy (NRT) on nicotine abstinence. METHODS: Two authors independently searched the PubMed, Embase, PsycInfo and Cochrane Central Register of Controlled Trials databases for articles published up to and including 10 July 2021. We included randomised controlled trials (RCTs) in which nicotine e-cigarettes were compared to NRT among current cigarette users. The primary outcome was abstaining from all nicotine-delivery devices. Secondary outcomes were 1) allocated product use (e-cigarettes or NRT) among successful cigarette quitters and 2) quitting cigarettes at the end of the trial using fixed-effect Mantel-Haenszel models. RESULTS: We included four RCTs representing 1598 adult participants (51.0% females). The mean age of participants in these studies ranged from 41 to 54 years, while average baseline smoking ranged from 14 to 21 cigarettes per day. Compared to NRT, e-cigarette use was associated with lower nicotine abstinence rates at the longest follow-up (risk ratio 0.50 (95% CI 0.32-0.77)). Among successful cigarette quitters, the risk of allocated product use by the end of the observational time was higher for e-cigarette users compared to NRT (risk ratio 8.94 (95% CI 3.98-20.07)). E-cigarette users had higher cigarette smoking cessation rates compared to NRT users (risk ratio 1.58 (95% CI 1.20-2.08)). CONCLUSIONS: The use of e-cigarettes as a therapeutic intervention for smoking cessation may lead to permanent nicotine dependence.

Assessment of Sleep and Sleepiness in Patients With Mental Disorders: Applicability of the German Version of the SCOPA-Sleep Questionnaire.

Sleep problems affect the majority of patients with mental disorders and are very clinically relevant. However, they are often not assessed and treated appropriately and, to date, there is no established screening routine for sleep disturbances in this specific patient group. For patients with Parkinson disease, the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-Sleep) questionnaire is widely used. This questionnaire has excellent psychometric properties. It consists of 2 scales for assessing nighttime sleep problems (NS) and daytime sleepiness (DS). As the items in the scales are not disease-specific, the goal of this study was to validate the SCOPA-Sleep for use in patients with mental disorders. A total of 370 German patients with mental disorders completed the SCOPA-Sleep as well as a multitude of other instruments for assessment of validity [eg, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS)]. For validity estimation, 627 healthy subjects were also included in this study. Internal consistency was good with coefficients of 0.806 and 0.772 for the SCOPA-NS and the SCOPA-DS. Factor analysis revealed 2 factors which could each be assigned to one of the subscales. Convergent validity was high with correlations of 0.672 between the SCOPA-NS and the PSQI and 0.644 between the SCOPA-DS and the ESS. The German version of the SCOPA-Sleep showed good diagnostic accuracy, resulting in an area under the receiver operating curve of 0.959 for the SCOPA-NS and 0.728 for the SCOPA-DS. For patients with mental disorders, the SCOPA-Sleep proved to be an economical, reliable, and valid instrument for assessing NS and DS which is well accepted by patients. It can be recommended for routine assessment of both NS and DS.

Use of Electronic Cigarettes as a Predictor of Cannabis Experimentation: A Longitudinal Study Among German Youth.

INTRODUCTION: Experimentation with e-cigarettes is rising among youth, and there are concerns that e-cigarettes could be a new risk factor for initiating substance use. This study aimed to investigate whether e-cigarette use longitudinally predicts experimentation with cannabis. AIMS AND METHODS: During 2017-2019, a prospective cohort study with an observation period of 18 months was conducted with 3040 students from Germany who had never used cannabis (mean age = 14.8, range: 13-18 years). A multiple Poisson regression was used to investigate whether e-cigarette use was an independent predictor of future cannabis use. RESULTS: Lifetime e-cigarette use was reported by 29.4% of the survey population (n = 894) at baseline, and 17.4% (n = 529) initiated cannabis use during the observation period. Among e-cigarette ever users, the initiation rate was 34.5% compared with 10.4% of never users. Results were robust to adjustment for age, sex, migrant status, type of school, sensation seeking, peer cannabis use, the use of alcohol and conventional cigarettes (ARR = 1.83; 95% CI: 1.48-2.25). Further analyses revealed that the association between e-cigarette use and cannabis experimentation was stronger among youth with low sensation-seeking scores (ARR = .77, CI: .61-.97) and no conventional cigarette use (ARR = .48, CI: .37-.64) at baseline. CONCLUSIONS: E-cigarette use is associated with a subsequent initiation of cannabis use. This association seems to be stronger for youth who have a lower risk for substance use in general. Future studies need to investigate whether this is only true for experimental or also more frequent cannabis use. IMPLICATIONS: The study indicates a prospective association between e-cigarette use and initiation of cannabis experimentation independent of other risk factors. It suggests that e-cigarette use is more strongly associated with cannabis initiation for youth with a lower propensity to use substances (low sensation-seekers and non-smokers).

Multichannel anodal tDCS over the left dorsolateral prefrontal cortex in a paediatric population.

Methodological studies investigating transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) in paediatric populations are limited. Therefore, we investigated in a paediatric population whether stimulation success of multichannel tDCS over the lDLPFC depends on concurrent task performance and individual head anatomy. In a randomised, sham-controlled, double-blind crossover study 22 healthy participants (10-17 years) received 2 mA multichannel anodal tDCS (atDCS) over the lDLPFC with and without a 2-back working memory (WM) task. After stimulation, the 2-back task and a Flanker task were performed. Resting state and task-related EEG were recorded. In 16 participants we calculated the individual electric field (E-field) distribution. Performance and neurophysiological activity in the 2-back task were not affected by atDCS. atDCS reduced reaction times in the Flanker task, independent of whether atDCS had been combined with the 2-back task. Flanker task related beta oscillation increased following stimulation without 2-back task performance. atDCS effects were not correlated with the E-field. We found no effect of multichannel atDCS over the lDLPFC on WM in children/adolescents but a transfer effect on interference control. While this effect on behaviour was independent of concurrent task performance, neurophysiological activity might be more sensitive to cognitive activation during stimulation. However, our results are limited by the small sample size, the lack of an active control group and variations in WM performance.

Differences in Food Craving in Individuals With Obesity With and Without Binge Eating Disorder.

Overeating behavior is supposedly a major contributing factor to weight gain and obesity. Binge eating disorder (BED) with reoccurring episodes of excessive overeating is strongly associated with obesity. Learning models of overeating behavior and BED assume that mere confrontation with food leads to a conditioned response that is experienced as food craving. Accordingly, individuals with obesity and BED were shown to have high trait food cravings. To date, little is known about differences in state food cravings and cue reactivity at the sight of palatable food in individuals with obesity and BED compared to individuals with obesity without BED. Therefore, the aim of our study was to examine differences in cue-induced, state and trait food cravings in people with obesity with and without BED. We found that all aspects of food cravings were more prevalent in individuals with obesity and BED than in individuals without BED. By implementing a food cue reactivity paradigm, our results show that individuals with obesity with BED have more cue-induced cravings than individuals with obesity without BED. Moreover, these cue-induced cravings in individuals with obesity and BED were highest for high-fat and high-sugar foods as opposed to low-calorie foods. Thus, our results emphasize the role of increased cue reactivity and craving at the sight of palatable foods in individuals with obesity and BED. Hence, our findings support etiological models of conditioned binge eating and are in line with interventions targeting cue reactivity in BED.

Dorsal and ventral striatum activity in individuals with buying-shopping disorder during cue-exposure: A functional magnetic resonance imaging study.

BACKGROUND AND AIMS: Buying-shopping disorder (BSD) is a clinical condition in which individuals lose control over their buying behaviour and continue buying despite negative consequences such as indebtedness, loss of family and friends. BSD has been considered a behavioural addiction and first studies provide evidence for cue-reactivity and craving as potential pathomechanisms. The current study aimed at investigating neural correlates of cue-reactivity and craving in individuals with BSD using functional magnetic resonance imaging (fMRI). METHODS: A cue-reactivity paradigm comprising individualised shopping-related and control cues was applied in n = 18 individuals diagnosed with BSD and n = 18 gender, age, and handedness matched control participants using fMRI. Outside the scanner, symptoms of BSD and craving reactions towards shopping (before and after the cue-reactivity paradigm) were assessed via questionnaires. FINDINGS: Higher subjective craving reactions towards shopping, prior and after exposure to shopping cues, were observed in individuals with BSD compared to control participants. Consistent with studies in addiction research, we found increased activations in the dorsal striatum for individuals with BSD compared to control participants during exposure to shopping cues. Activity in the ventral striatum was associated with symptoms of BSD in affected individuals, but not in control participants. CONCLUSIONS: Consistent with studies investigating cue-reactivity in substance-use and behavioural addictions, the association between cue-exposure and activities in reward-related brain structures such as the dorsal and ventral striatum in BSD participants may contribute to a neural explanation of why individuals experience irresistible urges to buy and lose control over their behaviour.

The Effect of Hunger and Satiety on Mood-Related Food Craving.

In addition to hunger, which results from food deprivation, fasting, or restrained eating, food craving is thought to be one of the major factors influencing eating behavior. Although food craving occurs in healthy humans with normal eating behavior, research suggests pronounced food craving to be a risk factor for binging food, which in turn might cause weight gain and obesity. In addition, negative mood seems to induce binge eating, although the underlying processes are not clearly understood. To examine these effects on momentary food craving more closely, we implemented a food cue-reactivity paradigm in 33 normal-weight females (mean age = 25.1 years, mean BMI = 21.6). Mood (negative vs. neutral) and state of food deprivation (hunger vs. satiety) were varied systematically. Self-rated craving was significantly higher in hungry compared to sated states. Moreover, in neutral mood, high-caloric foods modulated craving, i.e., hungry and sated participants preferred savory food and sweet food, respectively. In negative mood, this differential effect of savory and sweet items was absent. In summary, the state of hunger has a huge impact on food craving, which is further modulated by emotional state. Future research should consider hunger to be of high relevance for effects investigated in food-related paradigms. Our findings in healthy women of normal weight support etiological models of disturbed eating behavior and are in line with common interventions targeting eating schedules and mood regulation.

Imaginal Retraining Reduces Cigarette Smoking: A Randomized Controlled Study.

OBJECTIVES: Smoking is a highly prevalent addictive behavior with severe and life-shortening health consequences. This is the first study to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (ABM) (i.e., imaginal retraining) for the reduction of craving for tobacco and actual smoking behavior. METHODS: We randomized 345 smokers to imaginal retraining (self-help manual) or a control group (either active control or wait-list control). Assessments were carried out online. The treatment interval was 6 weeks. Craving for tobacco represented the primary outcome. The study was registered as DRKS00016860. RESULTS: Retention was 79.7% with no difference between groups. The intention-to-treat (ITT) analyses were significant for the primary outcome (Visual Analogue Scale on craving for tobacco) as well as subjective reduction of smoking (45.5 vs. 26.4%) in favor of imaginal retraining. In the treatment group, 47.6% performed the exercises at least once. This subgroup (per-protocol [PP] sample) showed a significant reduction in tobacco dependency as measured with the Cigarette Dependence Scale (short and long forms) and the Fagerström Test for Nicotine Dependence relative to controls. Number of daily cigarettes declined to a greater extent in imaginal retraining in the PP but not ITT analysis. A small dose-effect relationship emerged between craving and frequency of performance of the technique. CONCLUSION: When used regularly, imaginal retraining may reduce craving for tobacco and actual smoking behavior in a subgroup of smokers. In view of the large subgroup that did not read the manual or did not perform the exercises, alternative ways of conveying the imaginal retraining technique should be sought (e.g., demonstration via video clips). To conclude, imaginal retraining may represent a simple low-threshold technique to reduce smoking and assist current evidence-based treatment programs targeted at abstinence. It needs to be tested whether its mechanism of action deviates from standard ABM.

Fear of disease progression and relevant correlates in acute leukemia patients prior to allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Prior to hematopoietic stem cell transplantation (HSCT), and despite the high objective risks associated with HSCT, fear of progression (FoP) has only sparsely been studied in patients with acute leukemia until now. The aim of this study was the assessment of the prevalence of FoP, and any relevant correlates and typical concerns. METHODS: We included 59 adult patients with acute leukemia who were tested prior to their first HSCT during an in-patient stay. Patients completed self-report measures assessing FoP (Fear of Progression Questionnaire-Short Form, FoP-Q-SF) and relevant correlates of FoP (eg, patients' physical state, depression, psychosocial distress, or social support). RESULTS: About one third of the patients (35.6%; n = 21) had high FoP. Higher FoP was associated with previous cancer diagnosis, as well as depression, anxiety, reduced physical functioning, lower mental health-related quality of life, and lower positive social support. The greatest fears reported by these patients reflected common fears of cancer patients (eg, fear about leaving their families behind), but also specific fears related to the current situation (eg, fear of severe medical treatments during the course of the illness). CONCLUSIONS: This was the first study providing an extensive analysis of FoP in leukemia patients prior to the extreme situation of HSCT. FoP is frequent and of major clinical importance for these patients. Hence, we recommend that patients undergo routine screening for FoP, to identify highly distressed patients at an early stage, and to offer targeted support.

The importance of social relationships for brain tumor patients' quality of life: A case for the inclusion of the concept of disclosure in psycho-oncological care.

Purpose: Interpersonal factors are of major importance for cancer patients' physical and mental health. Brain tumor patients rank amongst those cancer patients with the highest psychosocial burden. Changes in language, cognition, and personality pose specific risk factors for impeding interpersonal functioning in this patient group. Despite this, role and relevance of social support including both supportive (e.g., emotional support) and detrimental interactions causing distress (e.g., critical remarks) are not well understood. Aims of this study were thus (1) to investigate the association of social support and patients' Health Related Quality of Life (HRQoL) and (2) to assess whether this relationship is mediated by the patients' disclosure behavior.Methods: Seventy-four ambulatory brain tumor patients (mean age 54 years; 58% women) completed the following self-report questionnaires: Illness-specific Social Support Scale (SSUK) for assessment of positive support and detrimental interactions, the Disclosure of Trauma Questionnaire (DTQ) for assessment of patients' disclosure behavior, and the Short-Form Health Survey (SF-8) for assessment of QoL.Findings: Detrimental social interactions were significantly related to patients' mental and physical well-being while positive support was not. Our results support a model in which patients perceiving detrimental social interactions show more difficulties in talking about illness-specific contents in a functional manner. This, in turn, was associated with a lower physical and mental HRQoL.Conclusions: This was the first study in which the close associations of detrimental social interactions, brain tumor patients' dysfunctional disclosure behavior and patients' mental as well as physical well-being were empiricially validated. Thus, dysfunctional disclosure behavior might pose a relevant therapeutic target when offering psycho-oncological support for brain tumor patients and their families.

Gray matter volume reductions in patients with schizophrenia: A replication study across two cultural backgrounds.

Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia.

Cessation of cannabis use: A retrospective cohort study.

Given recent findings of a worldwide increase in cannabis use, a better understanding of the factors associated with cannabis use is needed. Most previous studies have focused on factors that predict the initiation of cannabis use, but less is known about factors associated with cessation. The present study is a retrospective cohort study of 6467 current or former cannabis users aged 15 to 46 years (mean age 22.5, SD = 4.8). Data were collected via an online survey advertised in social media. All analyzed participants had used cannabis for at least three years. Approximately 16.3% (n = 1055) of the sample population had not used cannabis in the previous 12 months and were classified as quitters; all others (83.7%, n = 5412) reported at least monthly use. Cessation was predicted by older current age, being female, nonmigrant status, less sensation seeking, using psychological treatment, more peer cannabis use during youth and more negative first experience with cannabis. An additional predictor was a nonincrease in the frequency of cannabis use in the first three years of use, indicating that trajectories of cannabis use are set early on and might be used to identify risk groups for early preventive measures.

PTSD severity among emergency personnel: An investigation based on the Ehlers and Clark cognitive model.

OBJECTIVE: The relevance of both cognitive and interpersonal processes in predicting adjustment to potentially traumatic events has been highlighted in the literature. The aim of the present study was to investigate whether dysfunctional disclosure mediates the relationship between excessive negative appraisals and posttraumatic stress disorder (PTSD) symptomatology that is proposed in the cognitive PTSD model of Ehlers and Clark (2000). METHOD: A sample of 134 emergency service workers was interviewed to gain in-depth information regarding their experience of potentially traumatic events, and the following social interactions. Additionally, participants responded to the Disclosure of Trauma Questionnaire, the Posttraumatic Cognitions Inventory, and the Impact of Event Scale-Revised. RESULTS: Bootstrap mediation analyses revealed that the effect of negative trauma related appraisals on PTSD symptoms is partly mediated by dysfunctional disclosure. In particular, the two aspects of dysfunctional disclosure "reluctance to talk" and "excessive emotional reactions during disclosure" were of relevance in this model. The results remained stable even when controlling for potentially relevant sociodemographic and situational characteristics. CONCLUSIONS: Our results stress the importance of not only cognitive factors, but also interpersonal behavior in the development and maintenance of PTSD symptoms because we identified interpersonal risk factors (i.e., dysfunctional communicative strategies) to be relevant for PTSD elevation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Comparing birth experience and birth outcome of vaginal births between induced and spontaneous onset of labour: a prospective study.

PURPOSE: In developed countries, around 25% of all births involve labour induction. Studies have indicated that labour induction negatively influences the birth experience as well as the birth process. However, the impact of labour induction when only considering vaginal deliveries has not been studied yet, which was the purpose of the present study. METHODS: 186 women who gave birth vaginally took part in this prospective study. 95 women gave birth after spontaneous onset of labour (SL-group) and 91 women received a labour induction (LI-group). Eight to 72 h after birth, the women filled in the revised version of the standardised Childbirth Experience Questionnaire, which examines the birth experience in four dimensions (Own Capacity, Perceived Safety, Participation and Professional Support). Medical details regarding birth and fetal outcomes were taken from the medical records. RESULTS: Birth outcomes (the number of epidural anaesthesia, the duration of birth, birth risks and childbirth injuries) as well as fetal outcomes (APGAR after 1 and 5 min and arterial cord pH) did not differ between the groups. Regarding the subjective birth experience, the LI-group indicated significantly lower values for Perceived Safety and Participation compared to the SL-group, while there were no differences for the dimensions Own Capacity and Professional Support. DISCUSSION: Successful labour induction resulting in a vaginal birth did not negatively influence birth and fetal outcomes and only partly affected the women's birth experience. The negative impact of labour induction on the dimensions Perceived Safety and Participation should sensitize midwives in order to provide optimal support.

Adult patients with ADHD differ from healthy controls in implicit, but not explicit, emotion regulation

Background: There is increasing evidence that people with attention-deficit/hyperactivity disorder (ADHD) are impaired in emotion regulation, but psychophysiological and functional MRI data on emotion processing in adult patients with ADHD are scarce. We investigated the neural correlates of reappraisal as one of the most efficient emotion-regulation strategies. Methods: We included 30 adult patients with ADHD and 35 healthy controls in our study. We applied a well-established reappraisal paradigm in functional MRI and assessed behavioural emotion-regulation strategies with standardized questionnaires. We hypothesized that patients with ADHD would demonstrate impaired reappraisal related to reduced activations in the frontoparietal cognitive control network. Results: Despite our hypothesis, we found no significant activation differences in the neural reappraisal network between patients with ADHD and controls. As well, both groups revealed similar reappraisal success on the immediate behavioural ratings in the scanner. Interestingly, patients with ADHD revealed significantly increased activations in the dorsal and ventral anterior cingulate cortex (ACC) compared to controls when viewing negative > neutral pictures. These ACC activations were significantly correlated with the prevalence of habitual use of reappraisal in patients with ADHD only. Limitations: Patients withdrew medication only 24 hours before the experiment; we investigated negative, but not positive, emotion processing and regulation. Conclusion: Although emotion dysregulation is regarded as a core symptom of ADHD, explicit reappraisal does not seem to be impaired in adult patients. However, increased activation of the ACC implies stronger implicit emotion regulation induced by negative stimuli. This might be explained by emotional hyperresponsivity in patients with ADHD compared with controls.

Transient hippocampal CA1 lesions in humans impair pattern separation performance.

Day-to-day life involves the perception of events that resemble one another. For the sufficient encoding and retrieval of similar information, the hippocampus provides two essential computational processes. Pattern separation refers to the differentiation of overlapping memory representations, whereas pattern completion reactivates memories based on noisy or degraded input. Evidence from human and rodent studies suggest that pattern separation specifically relies on neuronal ensemble activity in hippocampal subnetworks in the dentate gyrus and CA3. Although a role for CA1 in pattern separation has been shown in animal models, its contribution in the human hippocampus remains elusive. In order to elucidate the contribution of CA1 neurons to pattern separation, we examined 14 patients with an acute transient global amnesia (TGA), a rare self-limiting dysfunction of the hippocampal system showing specific lesions to CA1. Patients' pattern separation performance was tested during the acute amnestic phase and follow-up using an established mnemonic similarity test. Patients in the acute phase showed a profound deficit in pattern separation (p < .05) as well as recognition memory (p < .001) that recovered during follow-up. Specifically, patients tested in a later stage of the amnesia were less impaired in pattern separation than in recognition memory. Considering the time dependency of lesion-associated hippocampal deficits in early and late acute stages of the TGA, we showed that the pattern separation function recovered significantly earlier than recognition memory. Our results provide causal evidence that hippocampal CA1 neurons are critical to pattern separation performance in humans.

Hippocampal Dentate Gyrus Atrophy Predicts Pattern Separation Impairment in Patients with LGI1 Encephalitis.

Day-to-day life involves the perception of events that resemble one another. For the sufficient encoding and correct retrieval of similar information, the hippocampus provides two essential cognitive processes. Pattern separation refers to the differentiation of similar input information, whereas pattern completion reactivates memory representations based on noisy or degraded stimuli. It has been shown that pattern separation specifically relies on the hippocampal dentate gyrus (DG), whereas pattern completion is performed within CA3 networks. Lesions to these hippocampal networks emerging in the course of neurological disorders may thus affect both processes. In anti-leucine-rich, glioma-inactivated 1 (LGI1) encephalitis it has been shown in animal models and human imaging studies that hippocampal DG and CA3 are preferentially involved in the pathophysiology process. Thus, in order to elucidate the structure-function relationship and contribution of hippocampal subfields to pattern separation, we examined patients (n = 15, age range: 36-77 years) with the rare LGI1 encephalitis showing lesions to hippocampal subfields. Patients were tested 3.53 ±â€¯0.65 years after the acute phase of the disease. Structural sequelae were determined by hippocampal subfield volumetry for the DG, CA1, and CA2/3. Patients showed an overall memory deficit including a significant reduction in pattern separation performance (p = 0.016). In volumetry, we found a global hippocampal volume reduction. The deficits in pattern separation performance were best predicted by the DG (p = 0.029), whereas CA1 was highly predictive of recognition memory deficits (p < 0.001). These results corroborate the framework of a regional specialization of hippocampal functions involved in cognitive processing.